José Luis Millán, Ph.D.[La Jolla]
These are the kinds of things we can achieve with active advocacy groups. It was very rewarding to see this therapy improve the quality of life of the first patient ever to receive it.
Dr. Millán studies the mechanisms that control normal skeletal mineralization and the pathophysiology of diverse calcification disorders.
Dr. Millán completed his Ph.D. studies at the University of Umeå, Sweden.
View All Publications
Rescue of severe infantile hypophosphatasia mice by AAV-mediated sustained expression of soluble alkaline phosphatase.
Matsumoto T, Miyake K, Yamamoto S, Orimo H, Miyake N, Odagaki Y, Adachi K, Iijima O, Narisawa S, Millán JL, Fukunaga Y, Shimada T
Hum Gene Ther. 2011 Nov;22(11):1355-64
José Luis Millán's Research Focus
Bone Mineralization Disorders, Colorectal Cancer, Testicular Cancer, Heart Disease, Peripheral Vascular Disease, Arthritis, Crohn’s Disease (Colitis), Metabolic Syndrome
Dr. Millán works on understanding the mechanisms that control normal skeletal mineralization and elucidating the pathophysiological abnormalities that lead to disease states such as hypophosphatasia, osteoarthritis, ankylosis and vascular calcification. These studies involve examining the function of the tissue-nonspecific alkaline phosphatase isozyme (TNAP), the nucleosidetriphosphate pyrophosphohydrolase-1 (NPP1) and the Ankylosis protein. These three molecules act in concert to regulate the extracellular concentrations of inorganic pyrophosphate (PPi), a potent inhibitor of mineralization. In turn, extracellular PPi (ePPi) concentrations regulate the expression of osteopontin (OPN), another important regulator of mineralization. Furthermore, OPN appears to regulate the concentrations of ePPi.
Current work focuses on testing the central hypothesis that the ePPi-mediated regulation of OPN and the OPN-mediated regulation of ePPi are linked counter-regulatory mechanisms that control the concentrations of these two important mineralization inhibitors, OPN and ePPi. Another project in the laboratory studies the mechanisms that control the initiation of bone mineral (hydroxyapatite) formation inside osteoblast-derived matrix vesicles and the role of TNAP and PHOSPHO1 in this process. Finally, these basic studies have identified novel therapeutic strategies for hypophosphatasia, osteoarthritis and vascular calcification. These translational studies involve the use of enzyme replacement therapy, small molecule inhibitors and cell/gene therapy to treat hypophosphatasia and the use of small molecule TNAP inhibitors to treat vascular calcification.
About José Luis Millán
José Luis Millán received his early training in clinical chemistry/biochemistry at the University of Buenos Aires, Argentina, and joined La Jolla Cancer Research Foundation, the predecessor of Sanford-Burnham Medical Research Institute, in 1977 as a trainee in Clinical enzymology. Dr. Millán then completed his Ph.D. studies at the University of Umeå, Sweden from 1981-1983 and after a period of postdoctoral training at the La Jolla Cancer Research Foundation he was appointed Assistant Professor in 1986 and promoted to Associate Professor in 1989 and to Full Professor in 1994 at the same institution. He held the Chair of Medical Genetics at the Department of Medical Biosciences, School of Medicine, Umeå University, Umeå, Sweden from 1995 to 2000. Dr. Millán is currently Professor at Sanford-Burnham Medical Research Institute, and he maintains adjunct affiliations with Umeå University and the Royal Academy of Medicine and Surgery, Murcia, Spain.